HIV-1 Viremia and Cancer Risk in 2.8 Million People: the South African HIV Cancer Match Study

Most research on HIV-1 viremia and cancer risk is from high-income countries. We evaluated the association between HIV-1 viremia and the risk of various cancer types among people with HIV (PWH) in South Africa. We analysed data from the South African HIV Cancer Match study, based on laboratory measurements from the National Health Laboratory Services and cancer records from the National Cancer Registry from 2004-2014. Using Cox proportional hazards models, we estimated hazard ratios (HR) for cancer incidence per unit increase in time-updated Log10 HIV-1 RNA viral load copies/mL. We created partially adjusted (sex, age, calendar year) and fully adjusted models (additionally including time-updated CD4 count). We included 2,770,200 PWH with 10,175 incident cancers; most common were cervical cancer (N=2,481), Kaposi sarcoma (N=1,902), breast cancer (N=1,063), and non-Hodgkin lymphoma (N=863). Hazard ratios for the association of HIV-1 viremia and cancer risk changed after partial and full adjustment and were generally attenuated for infection-related cancers but tended to increase for infection-unrelated cancers. In the fully adjusted model, HIV-1 viremia was associated with an increased risk of Kaposi sarcoma (HR per unit increase in Log10 HIV-1 RNA viral load: 1.38, 95% CI 1.35-1.42), leukemia (HR: 1.28, 95% CI 1.13-1.45), non-Hodgkin lymphoma (HR: 1.24, 95% CI 1.19-1.29), conjunctival cancer (HR: 1.19, 95% CI 1.11-1.25), and colorectal cancer (HR: 1.11, 95% CI 1.02-1.21). Associations with other cancer types were weaker or absent. Our findings underline the importance of sustained viral suppression for cancer prevention among PWH in South Africa.